9 - Disorders of Mineral Metabolism: Normal Homeostasis

Abstract

Calcium and phosphate homeostasis is maintained by the interaction of parathyroid hormone (PTH), calcitriol—the primary bioactive metabolite of vitamin D, the phosphatonin—fibroblast growth factor-23 (FGF23), and the thyroid gland product—calcitonin—acting in a coordinated manner upon the intestinal absorption of these ions, the proximal renal tubular reabsorption of filtered calcium and its excretion of phosphate, the deposition of these analytes into bone by the osteoblast, and their reabsorption from this site by the osteoclast. Calcium is essential for intracellular signal transduction, nerve conduction, blood clotting, and the strength and structural integrity of bone hydroxyapatite. Phosphate, second to calcium in abundance, is present in DNA and RNA nucleotides, requisite for energy generation, and a component of cell membranes, signal transduction pathways, and the bone mineral—hydroxyapatite. Phosphate is absorbed by the intestinal duodenum and jejunum, filtered through the renal glomerulus, reabsorbed by the proximal renal tubule or excreted in urine, and deposited into bone linked to calcium as hydroxyapatite from which site it may be reabsorbed by PTH and calcitriol. Under usual circumstances, the serum concentrations of calcium and phosphate are reciprocally related. Intact PTH is an 84-amino-acids (AA) peptide that is released from the parathyroid glands in response to declining serum concentrations of Ca2+ detected by the calcium sensing receptor expressed on the plasma membrane of the parathyroid gland chief cell whose message is transmitted through the seven transmembrane-heterotrimeric guanine nucleotide-binding PTH receptor that inhibits renal tubular reabsorption of filtered phosphate; increases synthesis of calcitriol, which enhances intestinal absorption of calcium; and activates osteoclastogenesis, thereby mobilizing calcium from bone . FGF23 inhibits renal tubular reabsorption of phosphate and decreases renal synthesis of calcitriol, thereby depressing intestinal absorption of calcium and phosphate; FGF23 increases the synthesis of water-soluble 1,24,25-trihydroxyvitamin D and thus its urinary excretion. Calcitonin, a 32 AA product of the parafollicular “C” cells of the thyroid gland, depresses serum calcium concentrations by inhibiting osteoclast function, thereby impairing its release from bone, and increasing its urinary excretion.